When an inflammatory reaction or tissue destruction has occurred in the body, it is diagnosed based on the detection of what is called an inflammatory marker as an index. One representative example of the marker is a C-reactive protein (hereinafter to be referred to as CRP). CRP is a serum protein secreted by the liver into the blood on affliction with autoimmune diseases such as rheumatoid arthritis, malignant tumor, primarily bacterial infectious diseases and the like. Therefore, CRP is known to show high values in patients with these diseases. However, since CRP values show high individual differences, it is a particularly useful index when observing the progression of the disease state of individual patients, rather than comparing against the standard value or the CRP values of others. CRP is generally measured immunologically by a method such as ELISA (Enzyme-Linked ImmunoSorbent Assay) and the like.
In the meantime, the left shift of white blood cells and an increase in the number of white blood cells occur in the early stages of inflammation. Therefore, it is clinically highly important to simultaneously measure not only CRP but also white blood cells.
The present inventors took note of the above-mentioned aspect and provided for the first time an apparatus for measuring blood cells and immunity from whole blood, which simultaneously enables measurement of white blood cell and CRP (JP-B-3477352, hereinafter to be referred to as patent document 1).
The apparatus described in patent document 1 is configured to classify white blood cells into 3 types. White blood cells can be divided into five kinds of cells: neutrophils, eosinophils, basophils, monocytes and lymphocytes. Of these, neutrophil, eosinophil and basophil are sometimes referred to collectively as granulocytes. In the apparatus for measuring blood cells and immunity from whole blood of the above-mentioned patent document 1, granulocytes, monocytes and lymphocytes are counted as white blood cells (i.e., classification into 3 types).
As shown in FIGS. 5(a), 5(b), and 6, in the apparatus for measuring blood cells and immunity from whole blood of the above-mentioned patent document 1, a specimen container 4 containing a specimen, a CRP cell 19, reagent containers (20, 21, 22) containing the reagents for CRP measurement, and blood cell counting-measuring cells (WBC cell 27 for white blood cells, RBC cell 28 for red blood cells) are aligned and disposed in a line in the horizontal direction. A single sampling nozzle 36 is controlled to move in the horizontal direction (positioning movement above each container and cells) and downward and upward movements (movements to go into and out from each container and cells) in a predetermined order. The sampling nozzle 36 is a thin and long tube also called a “needle”.
The processing steps and the order of movement of the sampling nozzle for the measurement of CRP and counting-measurement of blood cells are as shown in the flow chart of FIG. 7.
By these configurations, various processing steps for one specimen, such as the steps of [suction and discharging of specimen and CRP reagents, CRP measurement in CRP cell, blood cell counting and measurement in WBC cell and RBC cell, cleaning processing of each cell, cleaning processing of the outside of the nozzle where necessary after each processing step, and final cleaning processing of the inside and outside of the nozzle after the final step] are performed sequentially and full-automatically, and the whole processing steps require about 4 minutes per one specimen to complete.
In addition to the processing steps as mentioned above for one specimen, conventional apparatuses for measuring blood cells and immunity from whole blood are programmed to automatically perform routine cleanings of the CRP cell (container constituted to measure CRP) every time a predetermined number of specimens are processed.
Routine cleanings of the CRP cell are necessary for the following reasons.
For CRP measurement, a latex reagent for immunity measurement (e.g., anti-human CRP sensitized latex immunoreagent) is dispensed in the cell to perform a latex coagulating method, particularly, for example, the latex immunonephelometry RATE method. The latex reagent is an R3 reagent contained in a reagent container 22 in the examples of FIG. 5(a)-FIG. 7. In this case, latex particles contained in the latex reagent also attach to the inner wall surface of the CRP cell. The latex particles accompanying CRP relatively firmly attach to the inner wall surface and, as the number of treated specimens increases, the amount of the latex particles deposited on the inner wall surface increases. As a result, permeation of irradiation light for the CRP measurement is prohibited, and accurate measurement results cannot be obtained. Therefore, routine cleaning of the CRP cell is necessary.
Conventionally, to obtain accurate results of optical measurement, routine cleanings are performed for every specimen number of 15.
For routine cleanings of the CRP cell, a cleaning solution containing a cleaning agent for the latex reagent is used, so that the latex particles adhered to the inner wall surface of the cell as mentioned above can be removed. The cleaning solution is contained in a cleaning solution tank in the apparatus, and supplied to the CRP cell through an exclusive piping at the time of the aforementioned routine cleanings.
When the routine cleanings are started, a diluting liquid to be supplied into the CRP cell for rinsing the inside of the cell at the last stage of every CRP measurement is discharged, the next CRP measurement is discontinued, the cleaning solution in the aforementioned tank is supplied as it is (i.e., as undiluted solution) until the inside of the cell is filled, and the inner wall surface of the cell is immersed in the cleaning solution. This immersion state is maintained for 1-2 minutes, and the cleaning solution is discharged. Injection of the diluting liquid into and discharge thereof from the cell is repeated 6 or 7 times to perform rinsing, and the cleaning solution is thoroughly removed by the diluting liquid to prevent any remainder thereof. In this case, not only a simple rinsing movement involving injecting and discharging a fresh diluting liquid, but also a stirring movement by repeatedly sucking a diluting liquid injected into the cell from the cell, injecting diluting liquid again into the cell, and sucking the diluting liquid again from the cell may be added.
By a series of movements mentioned above, one routine cleaning takes about 6 minutes.
Routine cleanings of the CRP cell are free of problems and preferable for general tests. However, in an institution where a large number of specimens need to be measured, it is one of the factors that decrease the daily through-put.
In the constitution of conventional apparatuses for measuring blood cells and immunity from whole blood, the interval of routine cleanings of the CRP cell (number of specimens processed between the cleanings) and the cleaning steps performed in a single routine cleaning are appropriate and essential, and there is no room for increasing the interval of the routine cleanings, or shortening the time of single routine cleaning.
The problem of the present invention is to provide an apparatus for measuring blood cells and immunity from whole blood, which is capable of increasing the interval of the routine cleanings of the CRP cell and even eliminating the routine cleanings.